Sarah Sheibani

Delayed paracentesis is associated with increased in-hospital mortality in patients with spontaneous bacterial peritonitis.

OBJECTIVES:Spontaneous bacterial peritonitis (SBP) is associated with high mortality. Early paracentesis (EP) is essential for rapid diagnosis and optimal treatment. The aim of the study is to compare the outcomes of patients with SBP who received EP vs. delayed paracentesis (DP).METHODS:Consecutive patients who were diagnosed with SBP (ascites neutrophil count ≥250 cells/mm3 and clinical evidence of cirrhosis) <72 h from the first physician encounter at two centers were identified. EP was defined by receiving paracentesis <12 h and DP 12–72 h from hospitalization. Primary outcome was in-hospital mortality.RESULTS:The mean age of 239 patients with SBP was 53±10 years; mean Model for End-Stage Liver Disease (MELD) score was 22±9. In all, 98 (41%) patients who received DP had a higher in-hospital mortality (27% vs. 13%, P=0.007) compared with 141 (59%) who received EP. Furthermore, DP group had longer intensive care days (4.0±9.5 vs. 1.3±4.1, P=0.008), hospital days (13.0±14.7 vs. 8.4±7.4, P=0.005), and higher 3-month mortality (28/76, 37% vs. 21/98, 21%; P=0.03) compared with the EP group. Adjusting for MELD score ≥22 (adjusted odds ratio (AOR)=5.7, 95% confidence interval (CI)=1.8–18.5) and creatinine levels ≥1.5 mg/dl (AOR=3.2, 95% CI=1.4–7.2), DP was associated with increased in-hospital mortality (AOR=2.7, 95% CI=1.3–4.8). Each hour delay in paracentesis was associated with a 3.3% (95% CI=1.3–5.4%) increase in in-hospital mortality after adjusting for MELD score and creatinine levels.CONCLUSIONS:Hospitalized patients with SBP who received DP had a 2.7-fold increased risk of mortality adjusting for MELD score and renal dysfunction. Diagnostic paracentesis performed <12 h from hospitalization in patients with cirrhosis and ascites may improve short-term survival.

490 Prevalence of Antibodies to Adalimumab (ATA) and Correlation Between Ata and Low Serum Drug Concentration on CRP and Clinical Symptoms in a Prospective Sample of IBD Patients

BACKGROUND: Measurement of antibodies to infliximab (ATI) and the correlation observed between serum drug concentration and disease status have provided both insight into infliximab (IFX) immunogenicity and clinical utility to these markers for managing IBD patients on IFX. For adalimumab, such data are not readily available nor is clinical utility known. The prevalence of antibodies to adalimumab (ATA) in IBD patients is sparsely reported outside of one company sponsored clinical trial (2.6%). Correlation between ATA/ drug concentration and objective markers of inflammation (CRP) as well as clinical symptoms is poorly described. METHODS: An independent investigator-initiated cross-sectional study prospectively recruited 54 IBD patients on ADA (2 with ulcerative colitis) from a tertiary center to determine 1) prevalence of detectable ATA and drug concentration; 2) correlation between ATA /drug concentration and an objective measure of inflammation, C-reactive protein (CRP); and 3) whether stratified category of ATA/ drug concentration correlated with patients self-described symptoms (remission, response, active flare). Patients were approached based on use of ADA for Crohns or ulcerative colitis and not clinical status (remission, response, active). Questionnaire of symptoms, IBD history, ADA dosing, weight and CRP measurement were conducted within two weeks of ATA/drug concentration measurement. ATA/drug concentration blood draw was performed at trough, just prior to next ADA dose, and processed by Prometheus Laboratories. Detectable ATA was defined as .= 1U/ml and detectable drug as .=1 mcg/ml. RESULTS: The prevalence of detectable ATA was 22.2% (n=12/54) and detectable ADA concentration was 90.7% (n=49/54). Serum concentration of ,5 mcg/ml of ADA was associated with an elevated CRP (p=0.001). Detectable ATA was positively associated with an elevated CRP, and notably this correlation was independent of drug concentration (p=0.002) (Figure). Stratification of patients based on ATA/drug concentration demonstrated more active disease in patients with low drug concentration (,5 mcg/ml) and/or detectable ATA (p=0.01). CONCLUSION: Antibodies to adalimumab in ADA-treated IBD patients are more prevalent than reported in clinical trials and almost all patients on ADA have a detectable drug concentration. Both detectable ATA and ADA drug concentration ,5 mcg/ml have an important association with increased inflammation. The observation that detectable ATA correlates with elevated CRP independent of drug concentration is a novel finding and suggests preventing ATA may be the more critical of the two variables to address for maximizing clinical efficacy. That detectable ATA/ low drug concentration correlates with active disease suggests there may be clinical utility in obtaining these measurements, however longer-term data are needed.

Natural history of acute upper GI bleeding due to tumours: Short-term success and long-term recurrence with or without endoscopic therapy

Scant information is available regarding patients with upper gastrointestinal bleeding (UGIB) from tumours.

Causes of bleeding and outcomes in patients hospitalized with upper gastrointestinal bleeding.

Goals: To evaluate sources of upper gastrointestinal bleeding (UGIB) at an urban US hospital and compare them to sources at the same center 20 years ago, and to assess clinical outcomes related to source of UGIB. Background: Recent studies suggest changes in causes and outcomes of UGIB. Study: Consecutive patients with hematemesis, melena, and/or hematochezia undergoing upper endoscopy with an identified source at LA County+USC Medical Center from January 2005 to June 2011 were identified retrospectively. Results: Mean age of the 1929 patients was 52 years; 75% were male. A total of 1073 (55%) presented with hematemesis, 809 (42%) with melena alone, and 47 (2%) with hematochezia alone. The most common causes were ulcers in 654 patients (34%), varices in 633 (33%), and erosive esophagitis in 156 (8%), compared with 43%, 33%, and 2% in 1991. During hospitalization, 207 (10.7%) patients required repeat endoscopy for UGIB (10.6% for both ulcers and varices) and 129 (6.7%) died (5.2% for ulcers; 9.2% for varices). On multivariate analysis, hematemesis (OR=1.38; 95% CI, 1.04-1.88) and having insurance (OR=1.44; 95% CI, 1.07-1.94) were associated with repeat endoscopy for UGIB. Varices (OR=1.53; 95% CI, 1.05-2.22) and having insurance (OR=4.53; 95% CI, 2.84-7.24) were associated with mortality. Conclusion: Peptic ulcers decreased modestly over 2 decades, whereas varices continue as a common cause of UGIB at an urban hospital serving lower socioeconomic patients. Inpatient mortality, but not rebleeding requiring endoscopy, was higher with variceal than nonvariceal UGIB, indicating patients with variceal UGIB remain at risk of death from decompensation of underlying illness even after successful control of bleeding.

Randomized trial of 1-week versus 2-week intervals for endoscopic ligation in the treatment of patients with esophageal variceal bleeding.

The appropriate interval between ligation sessions for treatment of esophageal variceal bleeding is uncertain. The optimal interval would provide variceal eradication as rapidly as possible to lessen early rebleeding while minimizing ligation‐induced adverse events. We randomly assigned patients hospitalized with acute esophageal variceal bleeding who had successful ligation at presentation to repeat ligation at 1‐week or 2‐week intervals. Beta‐blocker therapy was also prescribed. Ligation was performed at the assigned interval until varices were eradicated and then at 3 and 9 months after eradication. The primary endpoint was the proportion of patients with variceal eradication at 4 weeks. Four‐week variceal eradication occurred more often in the 1‐week than in the 2‐week group: 37/45 (82%) versus 23/45 (51%); difference = 31%, 95% confidence interval 12%‐48%. Eradication occurred more rapidly in the 1‐week group (18.1 versus 30.8 days, difference = −12.7 days, 95% confidence interval −20.0 to −5.4 days). The mean number of endoscopies to achieve eradication or to the last endoscopy in those not achieving eradication was comparable in the 1‐week and 2‐week groups (2.3 versus 2.1), with the mean number of postponed ligation sessions 0.3 versus 0.1 (difference = 0.2, 95% confidence interval −0.02 to 0.4). Rebleeding at 4 weeks (4% versus 4%) and 8 weeks (11% versus 9%), dysphagia/odynophagia/chest pain (9% versus 2%), strictures (0% versus 0%), and mortality (7% versus 7%) were similar with 1‐week and 2‐week intervals. Conclusion: One‐week ligation intervals led to more rapid eradication than 2‐week intervals without an increase in complications or number of endoscopies and without a reduction in rebleeding or other clinical outcomes; the decision regarding ligation intervals may be individualized based on patient and physician preferences and local logistics and resources. (Hepatology 2016;64:549‐555)

Editorial: Are Thiopurines and Anti-TNFα Agents Safe to Use in Pregnant Patients With Inflammatory Bowel Disease?

Inflammatory bowel disease affects women in their peak reproductive years. Increased disease activity during pregnancy has been associated with adverse outcomes. Thus, it is recommended that immunosuppressant medications be continued during pregnancy. However, data regarding the safety of these medications during pregnancy are sparse and often conflicting. The study by Casanova et al. (1) adds to the growing evidence that the use of thiopurines and anti-TNFα agents during pregnancy does not increase the risk of birth defects. Results from prospective studies with longer follow-up are needed to fully understand the impact of thiopurines and anti-TNFα agents on child development and maturation of the immune system.

Preventive Health Care Among Postpartum Women With Inflammatory Bowel Disease: Results From the PIANO Registry

BACKGROUND Health care maintenance (HCM) is reduced among inflammatory bowel disease (IBD) patients. This study aims to characterize rates of HCM in a closely monitored subpopulation-postpartum women with IBD-and identify predictors of noncompliance. METHODS A national prospective pregnancy registry was utilized to collect completion rates of HCM recommendations (cervical cancer screening; osteoporosis screening; pneumococcal, hepatitis A, hepatitis B, and influenza vaccines). Completion of a recommendation at least once during follow-up was sufficient, except for influenza vaccine, which was assessed yearly. Patients were classified by drug exposures: immunomodulator (Group A), biologic (Group B), combination therapy (Group AB), and unexposed. Confounders assessed were steroid exposure, IBD flare, IBD care site, primary care provider (PCP) access, marital status, income, education level, and race. RESULTS There were 628 postpartum IBD women with at least 1 year of follow-up. HCM rates were as follows: cervical cancer screening (84%), osteoporosis screening (54%), pneumococcal (50%), hepatitis A (61%), hepatitis B (81%), and influenza (72%) vaccines. The unexposed group demonstrated lower pneumococcal vaccination rates than groups A, B, and AB. Group B demonstrated lower cervical cancer screening rates than the unexposed. PCP access and low education predicted hepatitis vaccine noncompliance. Unmarried status and low income predicted cervical cancer screening noncompliance. Low income predicted influenza vaccine noncompliance. CONCLUSIONS Postpartum women have multiple providers, yet they complete HCM at suboptimal rates. Risk factors include biologic exposure, unmarried status, low income, low education, and access to a PCP. Awareness among providers and patients is important and needs to be enhanced.

Reply: One-Week vs. Two-Week Intervals for Endoscopic Ligation.

risk of bleeding related to band ulcerations if the 1week interval is used given that this risk at 12 weeks was reported as 2 times higher than the risk associated with the 2-week interval (9% vs. 4%, respectively). Furthermore, ligation sessions were postponed because of band ulcerations more often in patients undergoing the 1-week, rather than the 2-week, interval (22% vs. 9%, respectively). Although variceal eradication at 4 weeks was noted to be faster in the 1-week group, the rebleeding rates at 1 month were not found to be lower than the 2-week group (2% vs. 0%, respectively). Final variceal eradication rates were also found to be similar in both groups at the end of 8 and 12 weeks (93%84%, respectively). An important flaw with this information is that the researchers did not provide any data about the number of bands used in each session, which will automatically affect the variceal eradication rates in their patients. At 8 and 12 weeks of eradication, the researchers noted a little bit higher bleeding rates in the 1-week than the 2-week group. Another issue with 1 week was higher rates of dysphagia, odynophagia, and chest pain in this group of patients than the 2week group (9% vs. 2%, respectively). Thus, this study clearly shows us that the 1-week interval, although seeming to have faster variceal eradication rates, is practically not superior to the 2-week counterpart because it did not lower rebleeding rates at 4, 8, and 12 weeks of follow-up and it resulted in more band ulcerations with more patients complaining of dysphagia, chest pain, and odynophagia.